Traditional Chinese medicine for prevention and treatment of hepatocellular carcinoma: A focus on epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant cancers worldwide. Epithelial-mesenchymal transition (EMT), which endows epithelial cells with mesenchymal properties, plays an important role in the early stages of metastasis. Conventional cancer therapies have promising effects, but issues remain, such as high rates of metastasis and drug resistance. Thus, exploring and evaluating new therapies is an urgent need. Traditional Chinese medicines (TCMs) have been acknowledged for their multi-target and coordinated intervention effects against HCC. Accumulating evidence indicates that TCM can inhibit the malignancy of cells and the progression of EMT in HCC. However, studies on the effects of TCM on EMT in HCC are scarce. In this review, we summarized recent developments in anti-EMT TCMs and formulae, focusing on their underlying pharmacological mechanisms, to provide a foundation for further research on the exact mechanisms through which TCM affects EMT in HCC.

Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway.

Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor which plays a key role in antioxidant and detoxification processes. Recent studies have reported that development of chemoresistance is associated with the constitutive activation of the Nrf2-mediated signaling pathway in many types of cancer cells. Here, we investigated whether Nrf2 was associated with drug resistant in doxorubicin resistant BEL-7402 (BEL-7402/ADM) cells, and if chrysin could reverse drug resistance in BEL-7402/ADM cells. We found that remarkable higher level of Nrf2 and its target proteins in BEL-7402/ADM cells compared to BEL-7402 cells. Similarly, intracellular Nrf2 protein level was significantly decreased and ADM resistance was partially reversed by Nrf2 siRNA in BEL-7402/ADM cells. chrysin is a potent Nrf2 inhibitor which sensitizes BEL-7402/ADM cells to ADM and increases intracellular concentration of ADM. Mechanistically, chrysin significantly reduced Nrf2 expression at both the mRNA and protein levels through down-regulating PI3K-Akt and ERK pathway. Consequently, expression of Nrf2-downstream genes HO-1, AKR1B10, and MRP5 were reduced and the Nrf2-dependent chemoresistance was suppressed. In conclusion, these results clearly indicate that activation of Nrf2 is associated with drug resistance in BEL-7402/ADM cells and chrysin may be an effective adjuvant sensitizer to reduce anticancer drug resistance by down-regulating Nrf2 signaling pathway.